The invention relates to a monitoring cell for performing a measurement in an NMR spectrometer of a reaction fluid produced in a reaction vessel, in particular for monitoring a chemical reaction by means of NMR spectroscopy, wherein the monitoring cell has the following components: a hollow sample probe for receiving the reaction fluid to be measured in the NMR spectrometer; an inlet transport capillary for receiving the reaction fluid from the reaction vessel and for transporting the reaction fluid from the reaction vessel to the sample probe; an outlet transport capillary for return transport of the reaction vessel from the sample probe to the reaction vessel; a device for conducting the temperature control fluid around the inlet and outlet transport capillaries, which comprises a feed line for delivering the temperature control fluid to the monitoring cell, and a return line for return of the temperature control fluid from the monitoring cell, the feed line being coaxially positioned within the return line; an adapter section through which the transport capillaries are fed; and an adapter head at the probe end of the adapter section, which is designed for coupling of the transport capillaries to the sample probe, the inlet capillary projecting into the sample probe and the adapter head separably connecting the sample probe to the adapter section. Such a monitoring cell, configured as an NMR flow cell, is known from U.S. Pat. No. 8,686,729 B2 or the parallel EP 2 407 796 B1.
The present invention relates generally to the field of continuous monitoring of chemical reactions by means of NMR spectroscopy.
NMR spectroscopy is a widespread measurement method by which chemical compounds can be analyzed. Usually in NMR spectroscopy, a sample to be measured in a sample tube is given in a sample probe, which is measured in an NMR spectrometer.
Chemical reaction monitoring essentially involves optimization of reaction parameters (temperature, pressure, solvent, catalyst . . . ) with the purpose of displacing the reaction equilibrium toward the product side and/or suppressing a faulty reaction. Thus, in order to maintain permanent reaction monitoring by means of NMR spectroscopy, samples must be taken regularly, which would constitute a great expense.
During the sample transfer, the reaction conditions (for example, the temperature and pressure) should be maintained so that the sample that is to be measured does not change. The time factor plays a significant role in this process.
Since the NMR spectrometer and the chemical reactor are spatially separated and the reaction monitoring is carried out in a closed system, the reaction mixture is pumped continuously from the reactor into the sample probe, where it is measured at regular intervals. The conditions in the transport system must be as close as possible to those predominating in the reaction vessel. This applies in particular to the reaction temperature.
In the initially cited U.S. Pat. No. 8,686,729 B2 or the parallel EP 2 407 796 B1, in each case a flow cell for chemical reaction monitoring by means of NMR spectroscopy is described. With the known device, the liquid reaction mixture is pumped continuously from the reactor to the NMR sample probe in the measurement device, where the liquid reaction mixture is measured.
The known system functions with a total of four coaxial tubes positioned within one another, the two inner capillaries comprising the transport capillaries for the reaction mixture. The two outer tubes are for circulating a temperature control fluid. The system consists basically of the following four parts:
1. Housing for reversal of the temperature control lines
2. Coupler section for decoupling of the transport capillaries from the temperature control lines
3. Ceramic head for separation of the transport capillaries into feed and return and
4. Sample probe (measurement cell), which contains only a feeder capillary of the reaction mixture.
In order to connect the four coaxial lines comprising the feed or return lines, several connecting sites are necessary, which results in great complexity of the system, as shown in the present FIG. 3 (taken from EP 2 407796 B1).
In addition, a coupling piece (see item 2 above) is provided in the known device, which decouples the capillaries of the reaction stream from the temperature control lines in order to feed the capillaries to the measurement cell. This creates a relatively large area in which the reaction mixture is not temperature-controlled, but exposed to room temperature. This is in particular a problem when working with thin capillaries and when the reaction temperature differs greatly from the room temperature. In this constellation, an exothermic chemical reaction can slow or alter the thermal equilibrium. For reactions that proceed at temperatures below 0° C., this can lead to an uncontrollable alteration of the sample condition at this exposed site.
It must therefore be ensured that the through flow in the heating or cooling circuit can be operated with commercially available circulation thermostats and the temperatures necessary for the reaction can be maintained over the entire length without significant loss. This means that resistors (such as T-connectors, for example) in the temperature control lines considerably reduce the flow, and thus cannot guarantee a temperature that remains the same within narrow limits over the entire length of the sample feed.
Furthermore, due to the known design, the volume of the return sample capillary is many times greater than that of the sample feed capillary, namely by a factor of around 5. Because of this, the circulation period until the sample to be measured is again transported back to the reactor is relatively long, which once again can negatively affect the reaction in the reactor.
Replacement of the sample probe (NMR flow tube) can only be carried out with a special tool. The connection must be irreversibly destroyed in the process (snap-cap, cut with a razor blade).
As mentioned, the temperature is an essential factor which greatly influences the reaction speed of chemical reactions. Herein lies the great difficulty of maintaining chemical equilibrium especially as regards the temperature. Further, the system for sampling must be structured as simply as possible, that is, it should be configured with as few connections and attachment sites as possible. Such sites are the ones that are frequently identified as weak links in the transport of fluids, where leaks can occur.
The invention is based on the relatively demanding and complex task of maintaining as uniform a temperature as possible in a monitoring cell of the above described type with inexpensive technical means in the feeder and return lines of the fluid measurement sample, in order not to influence the thermal equilibrium, and of simply designing the sampling system in such a way that as few as possible, as standardized as possible connection or attachment sites can be used, easily obtainable in commerce, while already existing devices must be easily upgradeable.